Regarding the spinal canal, the front (abdomen side) is composed of the vertebral body and the interspinal disk, the lateral is composed of the pedicle, and the rear (back side) is composed of the intervertebral joint and the spinal process. The inside space surrounded by the elements of the front, the lateral and the rear is called the spinal canal. The spinal cord is present within the spinal canal, and is the cauda equina like a horse's tail under around the first lumbar vertebra. When the cauda equina is pressed by spinal canal stenosis or the like to thereby worsen blood circulation of a blood vessel which supplies nutrition to the cauda equina running through the spinal canal, disorders of nervous functions are caused to present symptoms such as lumbago, lower limb pain, lower limb numbness, intermittent claudication, bladder and rectal disorder, sexual dysfunction or the like.
On the one hand, prostaglandins (hereinafter, abbreviated as PG) has been known as a metabolite in the arachidonate cascade. It has been known that the action has cyto-protective activity, uterine contractive activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awakening effect, a suppressive effect on gastric acid secretion, hypotensive activity and diuretic activity and so on.
A recent study has proved existence of various PGE subtype receptors possessing a different physiological or pharmacological role from each other. At present, four receptor subtypes are known and they are called EP1, EP2, EP3, and EP4 (Negishi M., et al., J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)).
It is described that a prostaglandin-like compound described in EP860430A1 has EP2 agonist action and is useful for prevention and/or treatment of immune diseases, asthma, abnormal bone formulation, neuron cell death, liver damage, abortion, premature birth or retinal neuropathy such as glaucoma etc. (Patent Reference 1).
It is described that a prostaglandin-like compound described in WO98/34916 has EP3 agonist action and is useful for prevention and/or treatment of liver diseases, Kidney disease, pancreatitis or myocardial infarction etc. (Patent Reference 2).
It is described that a prostaglandin-like compound described in WO2003/74483 has EP2 agonist action and is useful for prevention and/or treatment of immune diseases, allergic diseases, neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis, renal failure, circulatory diseases, systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, or bone diseases etc. (Patent Reference 3).
However, it is neither described nor indicated that the prostaglandin-like compound increases cauda equina blood flow without the influence on blood pressure.
[Patent Reference 1] EP860430A1
[Patent Reference 2] WO98/34916
[Patent Reference 3] WO2003/74483